Dr. Barry Kreiswirth gives an introduction on the research carried out in his laboratory.

Research
Summary

Dr. Kreiswirth is the founding director of the PHRI TB Center, a Professor of Medicine at Rutgers and has an adjunct faculty position in the Department of Medicine at New York University, is a senior lecturer at the Mailman School of Public Health at Columbia University and a visiting scientist at the Museum of Natural History. Dr Kreiswirth joined PHRI as a graduate student in 1978 in Dr. Richard Novick’s laboratory working on the molecular biology of Staphylococcus aureus and ultimately cloning and characterizing the genetic determinant responsible for toxic shock syndrome.

In 1992, in response to the New York City tuberculosis outbreaks, the PHRI TB Center was established under Dr. Kreiswirth’s direction as a genotyping laboratory to study the molecular epidemiology of tuberculosis. The center characterized the highly multidrug resistant strain “W” and beginning in 1992 it has genetically characterized over 27,000 M. tuberculosis isolates from global sources. Since its inception, the Center has worked closely with the Centers for Disease Control and Prevention and the New York City and New Jersey Departments of Health to integrate the tools of molecular biology with tuberculosis control efforts. The PHRI TB Center has extended its molecular epidemiological collaborations to global tuberculosis “hotspots” including the Russian prisons, the gold mines in Johannesburg and the XDR outbreak in KwaZulu-Natal, South Africa. Common to all studies is the characterization of drug resistance mutations and correlating phenotypic susceptibility assays with genetic alterations. The molecular epidemiological studies have created a rich genotypic database that has identified highly successful clones that have caused extensive disease throughout the United States and understanding their predominance and their microevolution has become a major effort in the laboratory.

The Kreiswirth laboratory is also focused on nosocomial infections and the emergence of antibiotic resistance and the research aims include the development of rapid genotyping methods for both molecular epidemiologic studies and to advance infection control strategies. The spa typing of S. aureus using the eGenomics analytical software has become a standard method to genotype the species to unravel suspected outbreaks and to determine phylogenetic relatedness. These studies have now established a biological foundation to extend the resolution of genotyping using whole genome sequencing and creating large comparative genomic databases. This work is now ongoing in collaboration with bioinformaticians and curators at the Sackler Institute of Comparative Genomics at the American Museum of Natural History.

The experiences in genotyping M. tuberculosis and S. aureus were brought to the emerging problem of carbapenem resistant Enterobacteriaceae which have rapidly spread across the New York Metropolitan area and which challenge both diagnostic and treatment protocols. In response, the PHRI TB Center has developed rapid molecular beacon-based genotypic assays to both identify and distinguish the predominant carbapenem resistant Klebsiella pneumoniae ST258 and to determine the genetic basis of its resistance. In parallel with the genomic studies to study the phylogeny of S. aureus, we are currently amassing genomic data for K. pneumoniae and the resistance plasmids they harbor to create comparative sequence databases that will be “mined” to create diagnostic platforms and targets for drug and vaccine development.

Video Presentations

In this presentation, laboratory members provide an overview of their laboratory
and discuss their research projects.